Supported Synthesis of Adenosine Nucleotides and Derivatives on a Benzene-Centered Tripodal Soluble Support

Abstract

The first soluble-phase synthesis of adenosine nucleotides including α,β and β,γ-methylene bisphosphonate analogues on a multi-pod support is reported. Anchoring of a 2’,3’-protected purine nucleoside to the tripodal support via the nucleobase was successfully achieved using a microwave assisted Cu(I)-catalyzed azide-alkyne cycloaddition. Then, phosphorylation was performed, followed by cleavage with aqueous ammonia to provide adenine derivatives, and finally deprotection. When using benzylamine instead of ammonia, a derivative with N6-benzylamine adenine as nucleobase was obtained. This methodology allows to access adenosine 5’-mono, di and triphosphates, as well as various analogues of pharmacological interest in modest to good yields.